RAINS Sydney 2016

Computed Tomography Contrast Media

Johnathan Hewis
Senior Lecturer in Medical Imaging
School of Dentistry & Health Sciences

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 Computed Tomography Contrast Media

• Pharmacology of iodinated contrast media

• Adverse effects of intravenous iodinated contrast media

• Practical considerations when administering intravenous

iodinated contrast media in CT

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salt 5-iodo-2-pyridone-N-acetate sodium

Thomas AMK, Banerjee AK, Busch U. Classic Papers in Modern

Diagnostic Radiology. Berlin, NY: Springer Verlag; 2005
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 Overview of CT contrast media

• IV iodinated e.g Omnipaque, Visipaque Extra-cellular

• Barium sulfate, diluted iodinated, water, lactulose

solution, polyethylene glycol (PEG) electrolyte solution,
Mucofalk, methylcellulose and milk…

• Air, C02

Positive Contrast Agents Negative Contrast Agents

Neutral Contrast Agents
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Pharmacology of iodinated contrast media

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 Why Iodine

• High atomic number; Z = 53 (barium; Z = 56)

• Tightly binds to benzene ring
• “K-edge effect” - iodine has a favorable K-absorption
edge at 33 keV (37 keV for barium)

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 Pharmacokinetics - ADME

• Absorption
• Movement of drug from site of administration into the blood
• Distribution
• Movement of the drug throughout the body (blood flow and
inherent drug properties)
• Metabolism
• Biotransformation (metabolites) enabling elimination
• Excretion
• Elimination of drug from tissue/organ of interest & body

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 Extra-Cellular Iodinated Contrast Media

Cell

Vessel
Cell

• Vasculature flooding with contrast agent Cell

• Blood enhancement as long a concentration of contrast remains in vessel

• Rapidly leaks across capillaries & into interstitum
 Pharmacokinetics of Extracellular Iodinated
Contrast Media
• After intravenous
administration
• Rapid distribution between
vascular & interstitial spaces
• Half life 3-60 mins
• Elimination by glomerular
filtration (95%)
• Blood & renal clearance similar
to creatinine
• High hydrophilicity
• No biotransformation
• Very low binding to plasma
proteins (< 5%)
• Pharmocokinetics
linear/proportional to dose
• Dialysable
• Negligible passage of BBB,
placental barrier and minimal
enteral absorption
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 Tri-iodinated Benzene Ring

• Six carbons numbered 1 to COOH

6 clockwise (kekule)
I 1 I
6 2
• C1 differentiates ionic from
non ionic 5 3
• Iodine at positions C2,C4 & R2 4 R1
C6
• C3 & C5 amide attachments I

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 COO- Na+

I 1 I
6 2
COOH
5 3
I 1 I R2 4 R1
6 2
I
5 3 COO-Meglumine *
R2 4 R1
I 1 I
I 6 2
Solubility
Factors increasing solubility: 5 3
•Salts (Na / Meg)
•Hydroxyl group R2 4 R1
•Amide group
* methylglucosamine
Dissociation can exert “electrical effects” I
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Parameter Sodium Meglumine

Solubility Less Better

Tolerance Less Better

BBB Crosses Does not

Vascular effects More Less

Viscosity Low High

Diuretic Less Strong

Bronchospasm No Yes

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Combination of two tri-iondinated benzene rings forms
an dimer (can be ionic or non-ionic)

COO- R5

I 1 I I 1 I
6 2 6 2

5 3 5 3
R3 4 4 R4

I I

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• Ionic dimer

• Large molecule

• High viscosity

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 Osmolality & Viscosity

Osmolality: Viscosity:
• Depends on no. particles • Particle size
• HOCM > LOCM • Dimer > Monomer
• Temperature
• Solvent

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 Osmolality

Osmolality directly responsible for:

• Vasodilation
• Sensations of heat, discomfort and pain
• Endothelial damage
• Thrombosis & thrombophlebitis
• Damage to BBB
• Hypervolemia (cardiovascular side effects)

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 Osmolality & Iodine:Particle Ratio

Iodinated Contrast Media

Ionic Non-ionic

Monomeric Dimeric Monomeric Dimeric

3:2 3:1 (6:2) 3:1 6:1

Hyper-osmolar Low osmolar Low osmolar Iso-osmolar

>1400 mOsm/kg 600 mOsm/kg 500-850 mOsm/kg 290 mOsm/kg

Urograffin : diatrizoate Hexabrix : ioxaglate Omnipaque : iohexol Isovist : iotrolan

Ultravist : iopromide Visipaque : iodixanol
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 Contrast Media Strength

As strength increases:
• Attenuation increases
• Viscosity increases
• Osmolality increases

• Tolerance potentially decreases

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Adverse Reactions to IV Iodinated Contrast Media

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 Adverse Reactions to
IV Iodinated Contrast Media

Types of reaction:
• Anaphylactoid or “allergic like” (idiosyncratic)
– activation, deactivation, or inhibition of a variety of vasoactive
substances or mediators e.g. histamine
• Non-anaphylactoid or “physiological” (more predictable)
– Chemotoxic
– Vasovagal - coincidental causation
– Idiopathic

• Combination; rapid progression

• Idiopathic

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 Adverse Reactions to
IV Iodinated Contrast Media

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 Adverse Reactions to
IV Iodinated Contrast Media

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 Adverse Reactions to
IV Iodinated Contrast Media

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 Identifying at risk patients

Risk Factors for Adverse Intravenous Contrast Media

Reactions:
• Previous contrast reaction
• Known allergies (allergic diathesis)
• Asthma
• Renal problems (dysfunction, diabetes, metformin therapy)
– Contrast induced nephrotoxicity (CIN)
– Nephrogenic systemic fibrosis (NSF)
• Heart problems (angina, CHF, cardiomyopathy)
– Volume & osmolality
• Anxiety

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 Renal Insufficiency or Dysfunction

Assessing renal function:

• Serum creatinine
– Influenced by age, gender, nutrition, muscle mass

• Calculated estimated glomerular filtration rate (eGFR)

– Formulae based in part on serum creatinine

• Both less reliable in unstable levels of renal dysfunction

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 Contrast Induced Nephropathy
• Defined as an increase in serum creatinine by 25% or 44umol/l
occurring within 3 days of the intravascular administration of contrast
medium in the absence of an alternative aetiology.
• May lead to renal failure

Risk factors:
• Patient related
– e GFR <60mls/min
– Diabetes Mellitus
– Dehydration
– Congestive cardiac failure
– Gout
– Myeloma
– Age >70
– Nephrotoxic drugs
• Contrast media related
– High Osmolarity agents
– Large doses of contrast media

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 Contrast Induced Nephropathy

Presentation:
• Fatigue
• Loss of appetite
• Nausea & vomiting
• Weakness
• Headaches

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 Incidence of Adverse Reactions

• True incidence unknown

• Most adverse effects are mild to moderate
• Many patients experience unrecorded physiologic
disturbances e.g. warmth or heat
• Low osmolality ionic and nonionic contrast media is
associated with a lower overall incidence of adverse
effects, particularly serious ones.
• Serious contrast reactions are rare using LOCM but
typically occur in the first 20 minutes

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Practical considerations when administering
intravenous iodinated contrast media in CT

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 Management

Collaboration between referrer, radiologist/nuclear med

physician & MRS practitioner
1. Assure contrast administration is appropriate for the
patient and the indication
– Patient risk versus potential benefit
– Imaging alternatives
– Clinically justified imaging request
2. Minimize risk of potential contrast reaction
3. Be fully prepared to treat a reaction should one occur

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 Standard safety precautions

• Identify at risk patients e.g. contrast questionnaire, renal function

• Contrast should only be administered by suitably trained personnel
• Staff trained to recognise and manage contrast reactions
• Patient observation; direct first 5 mins post injection, on premises for
15 mins (“at risk” 30 mins)
• Encourage hydration pre & post procedure
• Suitably trained staff to deal with severe adverse reactions
• Equipment available & regularly checked
– Resuscitation trolley
– Emergency drugs box available
– Oxygen available
– Suction available
• All adverse contrast reactions documented

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 Injecting IV Iodinated Contrast Media

1. Informed consent (oral or written?) & full cooperation

2. Effective communication with patient before, during &
after
3. If the patient reports pain or the sensation of swelling at
the injection site, injection should be discontinued
4. Direct monitoring of the venipuncture site by palpation
during the initial portion of the contrast medium injection

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IV infection entry routes

A. Catheter tip
B. Migration down catheter
surface
C. Catheter hub
D. Contaminated Infusate
E. Haematogenous Spread
F. Manipulation of I.V line

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Transfixation / Infiltration / Extravasation

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http://www.eatonhand.com/img/IMG00018.htm
Thromboembolism & Air Embolism

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 References

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